Nelson was working as a waiter at T.G.I. Friday's and doing occasional stand-up comedy when he was offered a job on Mystery Science Theater 3000, typing the suggestions in the writing room. The writers told him to feel free to make some comments on the movies they were watching, and Nelson impressed them so much with his wit and comedic timing that they made him a staff writer, and, later, head writer.

When series originator and host Joel Hodgson decided to leave the show half-way through the fifth season, he chose Nelson as his replacement, reportedly because he thought Nelson was a natural leader, a gifted comedian and a gifted muse, and also because Nelson simply looked good standing next to the show's puppets.[5]

In 2006, Nelson was appointed Chief Content Producer for Legend Films. He is responsible for building and leading the company's creative content, providing continuous commentaries, and developing other premium web-based programming. "I'm very excited. Legend Films is such a great fit for me—talented people who consistently put out a great product. Plus, there are Flaming Hot Cheetos in the lunch room vending machine. That made it an easy choice to join the team", enthused Nelson.[6]

One of the projects put together by Nelson and Legend Films was RiffTrax, a website offering the purchase of downloadable audio commentaries once again costarring two former MST3K cast members Kevin Murphy and Bill Corbett. The first commentary made available through the service was for Road House. In a September 2006 interview, Nelson said he felt that Rifftrax may be the closest thing to a reunion of the Mystery Science Theater 3000 team,[7] even though it has never featured Joel Hodgson, Trace Beaulieu, J. Elvis Weinstein or Frank Conniff as they are currently affiliated with Cinematic Titanic.

In 2013, Nelson agreed to do voiceover work for Armikrog.[8] Nelson voices the lead character, Tommynaut.[9]

He has described the role of Christianity in his family as "the very centerpiece of our lives. We're heavily involved in our church, my wife works with youth groups and churches as her profession, and almost every career and life decision I make depends upon it." He studies Christian apologetics and cites William Lane Craig and C.S. Lewis as influences.[10]